Pharmacokinetic study of neostigmine after intranasal and intravenous administration in the guinea pig.

It is well known that the nasal route may be an effective alternative to the administration of drugs poorly absorbed via oral administration. Thus an investigation of neostigmine bioavailability after nasal administration was undertaken. The neostigmine kinetic profiles after nasal and intravenous administration in the guinea pig have been compared, and results indicate good nasal absorption of neostigmine. At the same dose, no significant differences have been noticed between the two administration routes, as the area under the curve and the bioavailability index is close to 100%. Moreover nasal administration shows a longer plasmatic elimination compared with the i.v. route (t1/2 beta e.n. = 160.04 min; t1/2 beta i.v. = 23.35 min). Nasal absorption is observed to be dose-related. The present results suggest that nasal administration of neostigmine may be an effective clinical means in Myasthenia gravis therapy.

Effects of metoxibutropate, ibuprofen and guaiacol on the gastrointestinal system.

In previous studies we have shown that ibuprofen, guaiacol and the guaiacol ester of ibuprofen (I.N.N. metoxibutropate) are able to inhibit in-vitro prostaglandin synthesis. In the present study we have evaluated the effect of ibuprofen, guaiacol and metoxibutropate on the gastrointestinal system. Oral treatment with equimolar increasing doses of the three drugs produced a progressive inhibition of prostaglandin biosynthesis in the intestinal tract, without any effect on the rate of intestinal propulsion. Further studies evaluated the gastric tolerance of a molar dose of ibuprofen causing ulceration in 50% of the animals. After single and repeated administration of guaiacol and of the guaiacol ester of ibuprofen, the percentage of animals with gastric damage was very low and the index of ulceration seemed rather moderate. Our results show that although guaiacol is able to inhibit prostaglandin biosynthesis like a classic NSAID, it does not induce gastric damage. For these reasons it is justified to combine guaiacol with ibuprofen in order to reduce gastric erosions induced by a classic antiinflammatory drug.

Synthesis of some 5-azaflavones.

Within a plan of researches concerning drugs with anti-ulcer activity, a series of 5-azaflavones has been prepared. In this first communication we report the relevant synthesis obtained by cyclization of appropriate beta-diketones in HCOOH at the boiling point. The beta-diketones have been obtained by Claisen condensation, starting from methyl 3-hydroxypicolinate and from appropriate aromatic or heterocyclic methylketone, using NaH as base.

[Use of the "Sartorius" cutaneous absorption simulator for transdermal pharmaceutical forms of NSAIDs]. / Utilizzazione del simulatore di assorbimento cutaneo "Sartorius" per la messa a punto di forme farmaceutiche transdermiche contenenti FANS.

We report the results of the in vitro-release of the active ingredients (flurbiprofen and ibuprofen) from dermal form obtained by the Sartorius Absorption simulator SM16750. The results show that the choice of the excipients is basic. Using NSAID, the aqueous gel can be considered the suitable formulation to obtained a good in vitro-release. The quantities of the active ingredients released during the time are plotted in diagrams.

Antiulcer activity of some PG-like derivatives and their intermediates.

During a search on PG-like compounds as antiulcer drugs we synthetized some hetherocyclic derivatives. Some compounds of this series were found to be effective after oral administration in inhibiting restraint induced ulcers in the rat. Three of the most active compounds showed fairly good antiinflammatory activity in the carrageenin-induced rat paw oedema test and in the RPAR test.

Prostaglandins intermediates. Reduction of (E)-oxolactone by means of a chiral phase transfer catalyst.

Preparation of (15 S)-hydroxy derivative (1-b), a key intermediate in the synthesis of PG like compounds, by reduction the corresponding enone (2), is described. High yields in (S)-isomer was obtained by means of chiral phase-transfer catalyst: (-)-N-(1-dodecyl)-N-methylephedrinium bromide. Eleven ammonium quaternary salts derived from (-)-N-methylephedrine were prepared and tested as catalyst in the reduction of enone (2) with NaBH4. Synthesis of enone (2), from phosphonate (6) (via Wadsworth-Emmons reaction) is also described.